Massachusetts Alzheimer?s Disease Research Center: Neuropathology Core The Neuropathology Core serves both the Massachusetts ADRC (MADRC) and the Alzheimer research community by providing diagnostic validation of clinical assessments and providing tissue to investigators. Neuropathologic assessment has contributed to understanding heterogeneity associated with AD/ADRD, both across diseases and in terms of concurrent pathologic processes. The availability of tissue from the Core has been widely used by investigators working to accelerate toward a cure for AD/ADRC. To complete these missions, we have three sets of Aims. The first group (Aims 1-3), which are intended to marshal resources, is focused on the collection, diagnosis, collection of data, full reporting of findings ? to families and relevant physicians with a CLIA-compliant autopsy report through the Clinical Core, and to the Data Core for research purposes -- and the wide distribution of samples in support of the research community. Issues of heterogeneity are directly addressed in these efforts. The second group (Aims 4-6), which are intended to develop new strategies, incorporate innovate methods to determine the neuropathologic basis of imaging and fluid biomarkers in AD/ADRD, define the neuropathologic findings in subjects from clinical trials for AD/ADRD and develop new cellular resources from autopsy tissue including iPSCs (to be deposited at NCRAD) and isolated cell-type specific nuclei. As these three aims develop, we will be sharing insights and collaborating with other ADCs for validation and broad implementation. Disease heterogeneity will be addressed in both the assessment of the basis of biomarker signals and in the assessment of clinical trials subjects. The final group (Aims 7 & 8), which are intended to build the future, focus on training. First, there is a component of training basic and clinical researchers in aspects of the neuropathology of AD/ADRD as well as the intricacies and issues around tissue-based research. These efforts will be done in close collaboration with the REC. There are also efforts, done in collaboration with the ORE Core, in broad education about the importance of autopsy and brain donation to enhance our efforts to tackle AD/ADRD. The Neuropath Core interacts with all other components of the MADRC and with the broader scientific community to address critical problems to accelerate towards a cure for AD/ADRD.